The biological mechanisms underlying racial and socioeconomic disparities in periodontitis are inadequately conceptualized, rarely investigated and poorly understood. Research by our group and others leads to the novel hypothesis that the earlier onset and greater burden of periodontitis in African American and low socioeconomic groups, relative to white race and more advantaged groups, is mediated by an accelerated rate of biological aging. We propose to test this hypothesis using a nested case control study within the prospective cohort Atherosclerosis Risk in Communities (ARIC) Study. This offers an efficient epidemiologic design that capitalizes on the respective strengths of both the case control and the prospective cohort designs. This study will undertake secondary analysis of existing data and stored biospecimen. Periodontitis cases will be compared with healthy controls in the community-based biracial ARIC Study. In 1987-1989, adults aged 45-64 years were recruited from four U.S. communities: Forsyth County, North Carolina; Jackson, Mississippi; suburban Minneapolis, Minnesota; and Washington County, Maryland. Interviews and examinations collected information on sociodemographic characteristics, medical status and biological samples including blood. At Visit 4, when the cohort was aged 54-73 years, 6,691 ARIC Study participants received a full mouth periodontal examination. Cases will be 160 adults with severe periodontitis defined according to a modified case classification of the Centers for Disease Control and Prevention and the American Academy of Periodontology. Controls, who do not have periodontitis (n=160), will be frequency-matched to cases (n=160) by sex, age in years and ARIC field center/race. The biomarker of biological age is leukocyte telomere length (LTL) measured in genomic DNA of stored blood samples collected at Visit 2 (1990-1992) and Visit 4 (1996-1998). DNA will be isolated using PureGene extraction. Relative LTL will be measured using a well- established method of quantitative polymerase chain reaction. Cross-sectional evidence shows that shorter LTL is associated with higher risk for many chronic and age-related disorders. To date, few prospective studies have measured rates of telomere attrition over time and even fewer of these have compared telomere attrition rates between cases and healthy controls. The study has three specific aims; each aim builds on the prior aim to develop a complete picture of the association of LTL and periodontitis, the rate of LTL attritio in cases and controls, and the degree to race and SES may modify this relationship. Explanatory variables are established risk and protective indicators for periodontitis including smoking, diabetes, body mass index, diet, physical activity, systemic inflammation and oxidative stress. Achieving all three of the aims will yield a complete and nuanced picture of the effect of biological aging, mediated by social context, on periodontitis outcomes. PUBLIC HEALTH RELEVANCE: This is a unique opportunity to learn about variation in rates of biological aging between population subgroups, and the role of biological age in the progression of periodontal destruction. Providing insights into the biological basis of social disparities in periodontitis will stimulate new approaches in modalities aimed at reducing the magnitude of disparities in periodontitis and the burden of this disease on society by targeting modifiable aspects of biological aging.